Telomerase Activity in Reactive and Neoplastic Lymphoid Tissues: Infrequent Detection of Activity in Hodgkin's Disease

Abstract

We used the recently described sensitive and rapid detection assay called telomeric repeat amplification protocol (TRAP) to detect telomerase activity in lymphoblastoid (n = 5) and lymphoma cell lines (n = 7), hyperplastic lymph nodes (n = 6) and tonsils (n = 5), and tissues involved by non-Hodgkin's lymphoma (NHL) (n = 43) and Hodgkin's disease (HD) (n = 14). Clearly evident telomerase activity was found in all lymphoblastoid and lymphoma cell lines, and in 34 of 43 cases (80%) of NHL. These results were expected because of the proliferative and immortal nature of the cell lines and most malignant cells. However, positive results were obtained with the TRAP assay in all hyperplastic lymph nodes and tonsils, which raises the issue of derepression of telomerase activity during an immune response. Telomerase activity alone therefore does not distinguish malignant lymphoid proliferations from reactive states. Telomerase activity was detected in only 1 of 14 cases (7%) of lymphoid tissues involved by HD. Eight of the 13 negative cases were considered to be interpretable because of the lack (3 of 13 cases) or low level (5 of 13 cases) of telomerase inhibition. The five remaining cases could not be evaluated because of their telomerase inhibitor content. The findings imply either transient or very low levels of telomerase activity in HD or that HD for the greater part is a telomerase-independent neoplasm. Microdissection studies are needed to identify subsets of cells carrying telomerase activity in both reactive and neoplastic lymphoid tissues.

Telomerase activity in B-cell non-Hodgkin lymphoma

“…To our knowledge, this is the first large study of telomerase activity in various types of B‐NHLs. The results confirm the findings of previous smaller studies that showed telomerase activity to be present in vivo in most types of B‐cell lymphoma 7, 11, 13, 15, 16, 19. However, we found that low grade MZBCLs of extranodal, nodal, and splenic types lacked telomerase activity or had an extremely low level of telomerase.…”

“…Data regarding telomerase levels in MZBCLs are scarce in previously published studies. One study found an unquantified amount of telomerase in a single case of “monocytoid lymphoma” of an unspecified type and in one of two cases of “villous lymphocytic lymphoma” 11. In our study, the absence of telomerase activity was found to be unique to low grade marginal zone lymphomas.…”

“…Like other somatic cells, resting B lymphocytes generally possess little or no telomerase activity 8–10. However, telomerase activity has been found in some somatic lymphoid tissues11 and in precursor cells, specifically in rare, bone marrow‐derived, committed hematopoietic progenitor cells (CD34+ and CD38+)8, 12 as well as in rapidly dividing germinal center (GC) cells,10, 13 but not in pre‐ or postgerminal center B cells 10, 14. The telomerase positive B‐cell compartments differ from the others in that they have a high proliferative fraction 8, 12.…”

“…Several studies have demonstrated telomerase activity in various B‐NHLs 7, 11, 13, 15, 16. To date, however, no studies have assayed telomerase and proliferation indices in a large series of B‐NHLs in a systematic and quantitative manner.…”

Diagnostic Usefulness of Telomerase Activity in Nasopharyngeal Carcinoma

“…Human palatine tonsil was found to express telomerase activity that was as high as that in lymphoma. 19,20) This strong telomerase activity seemed to be derived from normal germinal centers, which were also commonly found in activated nasopharyngeal lymphoid tissues. It is thus reasonable that non-malignant nasopharyngeal tissue presenting an inflammatory focus, as well as many activated lymphoid cells, also expresses telomerase activity.…”